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. 2025 Jun;21(13):1625-1630.
doi: 10.1080/14796694.2025.2497719. Epub 2025 May 27.

E-VIRTUE: a study of enfortumab vedotin with or without pembrolizumab in rare genitourinary tumors-design and rationale

Elias B A Chandran  1 , Saad Atiq  1 , Nicholas Simon  1 , Daniel Girardi  1 , Lisa Ley  1 , Lisa Cordes  1 , Ruchi Patel  1 , Tzu-Fang Wang  1 , Andre R Kydd  1 , Bernadette Redd  1 , Salah Boudjadi  1 , Ian Stukes  1 , Rouf Banday  1 , Elizabeth Smith  1 , Dilara Akbulut  2 , Scot Niglio  3 , Sandeep Gurram  4 , Seth Steinberg  5 , Andrea B Apolo  1
Affiliations

E-VIRTUE: a study of enfortumab vedotin with or without pembrolizumab in rare genitourinary tumors-design and rationale

Elias B A Chandran et al. Future Oncol. 2025 Jun.

Abstract

NCT06041503 (ClinicalTrials.gov).

Keywords: Rare genitourinary tumors; antibody-drug conjugates; bladder adenocarcinoma; bladder squamous cell carcinoma; enfortumab vedotin; pembrolizumab; refractory testicular cancer; urachal adenocarcinoma.

Plain language summary

There is currently a lack of effective treatments for rare cancers arising in the urinary tract, such as adenocarcinomas and squamous cell carcinomas, and testicular cancers that have become resistant to multiple lines of chemotherapy (known as refractory testicular cancer). Published literature demonstrates that these cancers express the protein, nectin-4. Nectin-4 serves as an important target for the anticancer medication enfortumab vedotin (EV), which has been shown to be effective in treating bladder cancer that has spread beyond the bladder (known as metastatic bladder cancer); this cancer almost universally expresses nectin-4. The immunotherapy drug, pembrolizumab, has been shown to lengthen life in multiple cancer types including melanoma skin cancer, lung cancer, bladder cancer and kidney cancer. More recently, the combination of EV with pembrolizumab was proven to lengthen life in patients with metastatic bladder cancer. Given reports of nectin-4 expression in urinary tract adenocarcinomas and squamous cell carcinomas, and in refractory testicular cancer, we believe that EV with or without pembrolizumab will be effective in treating these tumors. The E-VIRTUE trial aims to evaluate EV with pembrolizumab in patients with these cancers who have never received immunotherapy and EV alone in patients who have previously received immunotherapy. The primary objective is to determine the percentage of patients with cancers that shrink by at least 30% in response to treatment. We will also report the percentage of tumors that express nectin-4 and evaluate new methods of assessing cancer, such as a blood test that identifies circulating tumor DNA.

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Conflict of interest statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

References

    1. Kantor AF, Hartge P, Hoover RN, et al. Epidemiological characteristics of squamous cell carcinoma and adenocarcinoma of the bladder. Cancer Res. 1988. Jul 1;48(13):3853–3855. - PubMed
    1. Aragon-Ching JB, Pagliaro LC.. New developments and challenges in rare genitourinary tumors: non-urothelial bladder cancers and squamous cell cancers of the penis. Am Soc Clin Oncol Educ Book. 2017;37(37):330–336. doi: 10.1200/EDBK_175558 - DOI - PubMed
    1. Yanagihara Y, Tanji N, Miura N, et al. Modified FOLFOX6 chemotherapy in patients with metastatic urachal cancer. Chemotherapy. 2013;59(6):402–406. doi: 10.1159/000362400 - DOI - PubMed
    1. Tatli AM, Uysal M, Goksu SS, et al. Complete response of primary bladder adenocarcinoma with the FOLFOX4 regimen. Urol Int. 2015;94(3):363–365. doi: 10.1159/000354332 - DOI - PubMed
    1. Fan FS, Yang CF. Advanced primary nonurachal adenocarcinoma of urinary bladder responding to modified FOLFOX6 and capecitabine: a case report. Oxf Med Case Reports. 2018. Aug;2018(8):omy050. doi: 10.1093/omcr/omy050 - DOI - PMC - PubMed

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